Quinolone & Fluoroquinolones

Quinolone & Fluoroquinolones

1. Quinolone & Fluoroquinolones Presented By Dr. Manoj Kumar Assistant Professor Department of Pharmacology Adesh Medical College & Hospital Ambala Can’t

2. The fluoroquinolones are a family of broad spectrum, systemic antibacterial agents that have been used widely as therapy of respiratory and urinary tract infections. Defination

3. Quinolone NALIDIXIC ACID Available for the management of UTI . Limited therapeutic ability. A/E – G I upset , rashes, neurological toxicity, hemolysis. Bacterial resistance.

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5. Fluroquinolones are bactericidal agents. They block bacterial DNA synthesis by inhibiting bacterial DNA gyrase and topoisomerase IV. Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA is required for normal transcription and replication Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division. Mechanism of Action

6. Mechanism of Resistance

7. Well absorbed orally, except norfloxacin. Bioavailability highest in gatifloxacin (>98%). Attend higher concentrations in urine, kidney, bone, genital tract, prostate, lung & bronchial mucosa. CSF penetration low except in pefloxacin. Elimination renal. Food delays absorption of ciprofloxacin, norfloxacin, pefloxacin & lomefloxacin. Have prolonged post antibiotic effect (6 hours). Pharmacokinetics

8. GIT :Nausea , abdominal discomfort, vomiting, diarrhoea. CNS :Headache , dizziness, agitation, alteration of mood, sleep disturbances, seizures, hallucinations, delirium. Hypersensitivity : Allergic reactions, rash, purities, rarely fever, urticaria, angioedema. Lomefloxacin, sparfloxacin and moxifloxacin cause phototoxicity . Sparfloxacin , moxifloxacin and gatifloxacin prolong QT interval on ECG. Crystalluria , Arthralgias and cartilage erosions with joint swellings. Adverse effects

9. Food, Antacids & Iron: Decrease absorption Theophylline, caffeine, warfarin : increase d serum concentration . Enzyme Inhibition. N SAIDs may increase C N S toxicity. (Seizures) Drug interactions

10. UTI TB Typhoid Diarrhoea Gonorrhoea Chancroid Respiratory tract infections. Eye infection. Anthrax. Neutropenic patients. Gram-negative septicaemias Bone, Joint, Soft tissue and intra-abdominal infections. Therapeutic Uses

11. Most commonly used (FQ). Very active against gram negative aerobes and Staphylococci. Food delays absorption. Bioavailability 60-70 % & t 1/2 3-5 hours. Excretion in urine and faces. Dose: 250 -750 mg 12hourly. Gonorrhoea: 500 mg BD. Chancroid : 500 mg BD for 3 days. Ciprofloxacin

12. Serum concentrations low outside genitourinary and intestinal tract. Food decreases absorption. Bioavailability 35-40 % & t 1/2 4.5 hours. No interaction with theophylline and caffeine. Useful in long term prophylaxis in recurrent UTI & travelling diarrhoea. Dose: 400 mg 12 hourly. Gonorrhoea : 800 mg OD. UTI prophylaxis: 200 mg OD. Norfloxacin

13. More active against some anaerobes, M. tuberculosis, M. leprae . Use in multidrug regimens in leprosy & TB (300-800 mg/day.) Food does not interfere with absorption. Penetrates CSF & t 1/2 5-7.5 hours. Bioavailability 95% Crosses BBB & excreted unchanged by the kidneys. No interaction with theophylline and caffeine. Chlamydia infection : 300 mg BD for 7 days. For gonorrhoea: 200 mg OD. Ofloxacin

14. Highly lipid soluble derivative of norfloxacin . Food delays absorption. Bioavailability 90% & t 1/2 8-13 hours. Better tissue penetration Higher concentration in CSF. Dose to be reduced in hepatic insufficiency. Increases levels of theophylline and caffeine. Dose: 400 mg 12 hourly. Pefloxacin

15. Oral bioavailability > 95% & Food delays absorption. Widely distributed & t 1/2 6-7.5 hours. Excreted unchanged over 24 hours. Incidence of phototoxicity highest. No interaction with theophylline and caffeine. Used in respiratory infection, urinary, skin and soft tissue infection. Dose: 400 mg OD . Levofloxacin

16. More active than ciprofloxacin against Staphylococci, Streptococci, Mycobacteria , Mycoplasma . Food does not interfere with absorption. Longest t 1/2 16-3O hours & Bioavailability 90% Phototoxicity seen in 8% patients, Increases QT interval on ECG . No interaction with theophylline, caffeine and warfarin . Banned in many countries including India. Dose: 200 mg OD . Sparfloxacin

17. Oral bioavailability > 90% & t 1/2 6-8 hours. Active as ofloxacin. CSF penetration good remains in the tissues for a longer period. Used in the treatment of urinary and respiratory tract infection. D ose: 500 mg OD . Lomefloxacin

18. Second generation FQ & Oral bioavailability >85 %. t 1/2 12hours & excretion in urine. Improved gram positive activity including penicillin-resistant S. pneumoniae and anaerobes. Less active against enterobacteriacea , Pseudomonas. Phototoxicity , CNS adverse effects common & prolongs QT interval on ECG. Not interfere with theophyllin or warfarin . Dose: 400 mg OD Moifloxcin

19. Second generation FQ Oral bioavailability 95 % & t 1/2 7-10 hours. Increased activity against penicillin resistant S. pneumonia. Excreted unchanged by the kidneys Can prolong QT interval on ECG. Used in respiratory and genitourinary infection. Banned in many countries, available in India. Dose: 400 mg OD. Gatifloxacin

20. Potent broad spectrum quinolone used topically. Good activity against gram positive bacteria and anaerobes. Can be absorbed systemically on topical application. Not recommended for simple infections like acne. Indicated for bacterial skin infections. Nadifloxacin

21. Children (not absolute) Pregnancy Lactation Epilepsy QTc prolongation Contraindication

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